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1 대한내과학회지 : 제 76 권제 3 호 2009 특집 (Special Review) - 주요알레르기질환의진단과치료 약물알레르기의진단 이화여자대학교의학전문대학원내과학교실 조영주 Update on the diagnosis of drug allergy Young Joo Cho, M.D. Department of Medicine, Division of Allergy and Clinical Immunology, Ewha Womans University School of Medicine, Seoul, Korea Hypersensitivity reactions to drugs are classified as immediate or nonimmediate reactions depending on the basis of time of appearance of reactions. Clinical and immunological studies suggest that immediate reaction is IgE-mediated and nonimmediate as type-iv (cell-mediated) reaction. For the evaluation of drug allergy, the patient's history is fundamental; the allergologic examination includes in-vivo and in-vitro tests selected on the basis of the clinical features. Prick, patch, and intradermal tests are the most readily available forms of allergy testing. However, there are some changes in the diagnostic evaluation of allergic reactions to beta-lactams, iodinated contrast media and local anaesthetics over the last several years. In immediate reactions, the sensitivity of skin testing and immunoassay is decreasing and for nonimmediated reactions, skin testing appears to be less sensitive than previous results. Drug provocation test is still the gold standard for identification of an causative drugs. The new diagnostic tools, such as the basophil activation test and the lymphocyte activation test, have been developed and are under validation. Based on the literature, the proposed algorithm may safely and rapidly distinguish between immediate-type and immediate drug reactions. This review provides an update to European Network for Drug Allergy (ENDA) document that gave the guidelines for the evaluation of drug allergy. The diagnosis of drug allergy needs to be standardized. (Korean J Med 76: , 2009) Key Words: Drug Allergy; Immediate reaction; Nonimmediate reaction; Skin test 약물을투여하여원하지않는반응이나타날때이를약물의부작용이라고한다. 약물의부작용은약물의약리학적, 혹은독작용에의해나타나는예측가능한반응과예측할수없는이상반응으로나누어지며, 약물알레르기혹은약물과민반응은예측불가능한반응으로일부를제외하곤면역학적인기전에의하여생긴다. 약물알레르기반응은 IgE에의한즉시형반응과 T 세포매개성반응인비즉시형 ( 혹은지연성 ) 반응으로나눌수있다 1). 즉시형반응은약물투여후 1 시간이내에나타나는반응으로두드러기, 혈관부종, 비염기관지경련, 아나필락틱쇼크중의하나혹은복합적으로나타나며, 비즉시형에는반구진성발진 (maculopapular), 지연성으로나타나는두드러기 / 혈관 부종, 고정약진, exfoliative dermatitis, acute generalized exanthemattous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) Stevens- Johnson syndrome, toxic epidermal necrolysis (TEN) 이이에속한다 2). 약물알레르기, 과민반응은오래전부터관심들을갖고연구되어왔으나아직잘알려지지않은부분이많다. 계속해서새로운물질이개발되고, 약물의첨가물질역시늘어나고있는상태로지속적으로새로운생물학적물질에대한과민반응이증가하고있으며, 아직안전하고확실한진단방법이없는실정이다 3). 약물알레르기와과민반응의진단은표준화가되어야하며최근에는유럽알레르기및임상면역학회를중심으로결성된 European Network for Drug

2 - Young Joo Cho. Update on the diagnosis of drug allergy - Table 1. Diagnostic tests of hypersensitivity reactions to drugs Type of reaction Immediate Nonimmediate Type of test In vitro In vivo In vitro In vivo Specific IgE assays Flow cytometric basophil activation tests Skin tests Drug provocation tests Lymphocyte transformatior or activation tests Delayed-reading intradermal tests patch tests Drug provocation test From Romano A, Demoly P:Recent advances in the diagnosis of drug allergy. Cur Opinion Allergy and Clinic Immunol. 7, , 2007 Allergy (ENDA) 에의하여표준화작업이진행되었으며 2009 년에 standard operating procedures (SOPs) 으로발표되었다 4). 아직우리나라에서는이런작업이이루어지지않아서지침서가발간되지는않았지만, 알레르기전문가들에의하여우리나라의실정이맞는지침서가만들어질것으로기대된다. 아스피린에대한이상반응은가성알레르기반응으로그기전이다른면역반응과다르고자체로내용이많아본문에서는다루지않았다. 주로전형적인 IgE 매개성과 T 세포매개성과민반응을중심으로최근에표준화가작업이이루어진 ENDA에서제안된자료와최근에발표된보고를중심으로기술하고자한다. 병력, 임상적검사단계 약물알레르기진단의가장중요한정보를주는단계로아주철저하게임상적병력을모아야한다. 이과정에서중요한것은일정한양식을가지고이를바탕으로병력을작성하는것이다. 현재유럽의 ENDA 에서 1999년에제시한문진챠트가추천되고있으며여러나라에서각나라의언어로변형하여사용하고있다 5). 자세한문진후반응이즉시형인지비즉시형인지판단하여다음단계의검사로진행한다 ( 표 1) 6). 또한환자가한가지약이아니라여러가지의약을병용하고있을때에는좀더자세한문진표및기록, 병력의검토가필요하며다음과같은단계로검사를진행한다 7). 1 단계 : 임상자료수집 a. 약물반응의병력 b. 아토피여부 c. 동시에들어간약물의시작시간, 중지한시간용량의변화 d. 약물반응과관련이있을증후, 증상, 유용한비특이적인검사소견 (ESR, 호산구수, tryptase, proteinuria 등 ) 의시간별로기록 2 단계 : 가능한약물의범위를좁혀나간다. a. 약물의시작과중단시점, 증상발현과의관계 b. 반응이심해지는단계의약제 3 단계 : 가능성있는약제의다른약리역학적인연구결과들을기초로한순위부여 4 단계 : 가장가능성있는약제를중단하고반응의변화를관찰 5 단계 : IgE 반응여부판단하기위한피부반응시험실시단, 아나필락틱쇼크후 14일이내이거나 haptenic 약제의경우에는음성결과를무시한다. 6 단계 : 원인으로가능성있는약제의재투여피부반응이음성인경우낮은용량으로시작하여점진적으로증량, 만약반응이 IgE에의한반응이거나피부반응양성인경우탈감작시도 IgE 매개성즉시형반응의시험및검사최근 ENDA에서제안한 IgE 매개성반응의진단의알고리즘을그림 1, 2로정리하였다 6). 그림 1은간단한알고리즘은하루안에끝나는장점이있지만, 반응의선택성을구분하는데에문제가있고, 그림 2는 2일이걸리지만전자의단점이보안되는장점이있다. 1. 피부반응시험피부반응시험은높은예민도로다른검사들로대체될수없는약물알레르기진단의가장중요한검사이다. Beta lactams(bls) 계약물이단자나피내시험과같은피부반응으로진단에가치가잘확립되어있으며 8-10), penicillin의피부반응의예측치는표 2에정리한바와같다 7). 이외에피부반응시험이유용한약물로보고된것은 cephalosporins, 국소마취제, 헤파린이있으며, 조영제의경우즉시형반응인경우피부반응시험으로진단적가치가있다고보고되고있다 6). 약물알레르기에서 BLs은아직까지제일흔한원인약제

3 - 대한내과학회지 : 제 76 권제 3 호통권제 583 호 Figure 1. Short algorithm for the diagnosis of immediate allergic reactions to betalactams. From Blanca M, Romano A, Torres MJ, et al. Update on the evaluation of hypersensitivity reactions to betalactams. Allergy. 64: , 2009 Figure 2. Long algorithm for the diagnosis of immediate allergic reactions to betalactams. From Blanca M, Romano A, Torres MJ, et al. Update on the evaluation of hypersensitivity reactions to betalactams. Allergy. 64: , 2009 Table 2. Predictive value of penicillin skin testing Prior reaction Penicillin skin tests IgE-dependent reaction (%) Any immunologic reaction (%) Any All histories Anaphylaxis Urticaria Exanthem Other/unknown None Positive Negative Positive Negative 50~80 * < * Limited data from inadvertent treatment or provocational challenge Data from large, outpatient, sexually transmitted disease clinical study. Data unavailable for major and minor determinant testing. Early studies with penicilloyl polylysine in history-negative subjects indicated a low reaction rate (5.5%). From Middleton's Allergy: Principles and Practice, 7th Edition 이다. BLs은감작시키고노출후임상반응을야기하려면운반분자와결합해야하며 carbonyl group과의결합을통하여 benzylpenicilloyl determinant (BPO) 로된다 12). 현재사용되는 BLs은 Benzylpenicillin (BP), amoxacillin (AX) cephalosporins 등이다. 약물알레르기를일으키는항원이되는가장중요한구조는 side chain으로알려져있다. ENDA는약물반응을진단하는알고리즘을제안하고있지만, 아직까지진단에많은어려움이있다. 즉, 전형적인 major, minor BP detreminants를검사할수있는시약의생산이거의중단되었고, 여러가지 in vitro 실험은시간과비용실험이복잡하여일상적으로적용하는데에문제를가지고있다. 피부반응시험은 IgE 매개알레르기반응을진단하는데에가장기본적인검사법이지만 BLs의에서몇가지고려되어야할중요한점을지적하면다음과같다 11). Major와 minor determinants의시장에서의소멸 ; 전통적인 BP reagents(ppl, MDM) 으로피부반응시험을하는것이기본이라하였지만그동안이검사시약을생산하였던회사가 2004년이후생산을중지하고스페인한곳에서판매하고있다 13, 14). Haptens: Hapten 들중어떤것을기본을검사할것인가에대하여 ENDA에서는어떤 BLs에알레르기기있는지확실하지않을때원인으로가장의심이되는 determinants에

4 - 조영주. 약물알레르기의진단 - 추가로 PPL, MDM, AX로시행하는것을추천하고있다. 최근발표된바에의하면 BP은 10,000 IU/mL 까지시행하는것이예민도를높인다고하며피부반응시험에서 PPL과 MDM 이음성인경우 BP도검사되어야한다 15). 민감도와특이도 : 피부반응도의예민도는알레르기반응후시간경과에따라변화하는데반응이나타난다음해에는 PPL과 MDM 에 77.7% 의양성율이보이나몇년후에는 PPL은 42.1%, MDM 은 22.1% 로감소한다고보고되었다 16, 17). 하지만이런 PPL과 MDM에대한양성율의감소는 AX의민감도의증가로이어진다 18). AX에대한특이도는시간이지나가도큰차이가없다. Cephalosporin을보면, 최근의두연구에서민감도는 30.7~69.7% 로이는앞으로좀더많은대상으로연구가진행되어야신빙성있는민감도및특이도가나올것이다 19, 20). 알레르기검사후의재감작 : 약물유발검사후약물의치료, 피부반응검사후에피부반응이음성이던환자에서 1 달이지나다시시행한검사에서양성으로되는율이 0.9% 에서 27.9% 까지보고되었다 21, 22). 이런현상은주로이전에 penicillin에대한즉시형반응을경험하였던환자에게서나타난다. 따라서이전에 BLs에알레르기반응이있었던환자에서피부반응시험이음성일때는다시피부반응시험과약물유발시험등을재시행하는것이추천되고있다. 피부반응시험후의전신반응 : 검사받은환자의 1.3%, 양성을보인환자는 8.8% 가전신반응이생겼다고한다 23). 아나필락시반응이중요한위험인자 24) 로피부반응시험시항상응급조치할수있는장비와약제, 농도의조절후 1시간관찰을하는원칙을지켜야하며여러 determinants로검사하는경우시간간격을충분히뛰어서시행해야한다. 2. In vitro 시험특이 IgE를측정하는두가지주요검사방법이있다. 하나는 immunoassay 방법이고다른하나는 hapten에의한호염기구의활성화기전을기본으로히스타민이나루코트리엔과같은화학매체를측정하는것과호염기구활성화지표를검사하는것이있다. 과거 10여년간을이에대한검사법의개발및발전을위해노력을하였지만, in vivo 시험보다더낳은방법은아직확립되지못하여서연구를목적으로하는경우와아주심한과민반응인경우 1차로시행하는것으로이용되고있다. Immunochemical assays 상품으로나와있어가장많이이용되는것이 Phadia CAP System FEIA방법 (Phadia, Uppsala, Sweden) 인데이는 AX나 BP-derived 약물에대해피부반응시험에서양성인환자에서예민도는 48~54%, 특이도는 95~100% 로보고되고있다 25). RAST 의경우도예민도는 42.9~75% 이고, 특이도는 66~83% 로보고되었고, 특히아나필락틱쇼크의경우에예민도가높다 26). 이런방법들은예민도와특이도받아들일만하지만, 그예민도를높이기위한방법의개선이필요하다. 하지만 BLs에대한즉시형반응의병력이있는데피부반응에서음성으로나오고혈청특이 IgE는양성으로나오는경우도있으므로피부반응시험과혈청특이 IgE를같이검사하는것이약물알레르기의진단에예민도를높이는길일것이다. Cellular tests: 알레르겐으로세포를자극하여 sulpidoleukotrienes (LTC4, LKD4, LTE4) 을측정하는방법은예민도와특이도가낮아서진단에유용하지못하다. 하지만호염기구를자극하여활성화된호염기구의세포표면에증가하는 CD63을유세포측정기로측정하는 BAT (Basophil activation Test) 는 50% 의예민도와 93% 의특이도를보이고특히약물유발시험에서양성을보이고피부반응시험과 immunoassays 에서도음성을보인환자의 14.3% 에서양성을보였다 27, 28). 유럽의다기관연구에서 BAT는 BLs에대한알레르기반응을진단하는데에중요한검사로부각되고있으며, 특히 immunoassays가유용하지못하는 cephalosporins의경우중요한진단법이다. 3. 약물유발시험 (Drug provocationtests; DPT) DPT는약물알레르기에서원인약물을확진할수있는방법으로 ENDA에서도나타나는반응의중증의정도에따라시작하는약물의농도를조정하면서시행할것을권하고있다. 특히 BLs간의교차항원성을확인하고자할때에유용하다 29, 30). 4. 교차항원성의판단과거에 penicillin에약물알레르기반응을보였던환자에서 cephalosporins은안전하게투약할수있는지를확인하는것이중요한이슈이다. Cephalosporins 중 1세대의경우구조적으로 penicillin과유사점이많아서화학적인구조가상이한점이많은 2, 3세대보다교차반응이나타날확률이높다. side chain-특이적반응의경우 AX에선택적으로반응하는경우와 cephalosporins 중에서같은 side chain을갖고있는경우교차항원성이높게나타난다 19, 31)

5 - The Korean Journal of Medicine: Vol. 76, No. 3, Figure 3. Algorithm for the diagnosis of nonimmediate allergic reactions to betalactams. From Blanca M, Romano A, Torres MJ, et al. Update on the evaluation of hypersensitivity reactions to betalactams. Allergy. 64: , 2009 피부반응시험이나 in vitro 시험이나교차항원성을정확히보여주지못하여연구마다대상마다서로다른결과들을보여준다. 염두에두어야할것은교차항원성에서가장중요한것은 R1-side chain으로같은 R1구조를갖고있는 ceftriaxone, cefotaxime, cefepime은서로교차반응을보이는경우가많다. 그럼에도불구하고어떤환자는 side chain이다른 cephalosporins에교차반응을보이는데이는공통인구조에특이항체가반응하기때문이다 18, 20, 32). BLs 중 penicillin과 carbapenem monobactam에대한교차반응에대해서재고해야된다는의견들이대두되고있다. 1950~2008까지의보고된논문들을근거로분석한보고서에서 imipenam, clastatin과 meropenem은 penicillins에즉시형반응을보인환자의 1% 이내에서피부반응양성율을보인다고한다. Monobactam 과페니실린은교차반응이없다고알려져왔는데물로교차반응이거의없긴하지만, ceftazidime과 aztreonam은 side chains이같아서교차반응이드물게올수도있다 33, 34). 결론적으로 ENDA에서는 penicillin-알레르기환자에게대체하여사용할수있는 BLs으로 cephalosporin, carbapenem, aztrenam에대한피부반응시험을꼭시행하여음성인경우사용할항생제를용량을서서히올려가며사용할것을권고하고있다. T cell 매개성반응 : 비즉시형반응비즉시형반응은약을투여후짧게는 1시간후부터 2 4~48시간이후에나타나며, BLs에가장흔한약물반응인구진성홍반혹은약진 (maculopapular, mobilliform,drug rash) 의기전으로알려져있다 35). 이외에흔하지는않지만중증의반응으로 exfoliative dermatitis, AGEP, DRESS, Stevens- Johnson syndrome, toxic TEN 등의원인기전이다 2). 반응부위조직검사에서주로 CD4세포, CD8 세포가침윤되어있으며, Th1의 cytokine의발현이증가되어있어서 T 세포가중심인면역기전으로인한것으로생각되나 35, 36) 아직확실하게그면역기전이다밝혀진것이아니므로진단방법도확립되지못하였다. 약물의 T세포매개반응을진단하는것은특히바이러스감염과연관해서오는경우가흔하고임상상도다양하다 37, 38). 1. 피부반응시험피내시험의지연판독, 첩포시험을시행할수있으나그예민도가 2.6% 에서 37.8% 로보고마다다양하며최근에더정밀하게짜여진연구들에서는그예민도가더낮게보고되고있다 39, 40)

6 - Young Joo Cho. Update on the diagnosis of drug allergy - 2. In vitro tests Lymphocyte transforming test (LTT) 가가장널리시행되는실험실방법이다. 이는예민도 74%, 특이도 85% 정도로보고된바있으나주로연구목적으로시행되고있을뿐이다 41). 3. 약물유발시험유일한진단법은약물유발시험이다. 이는 AGEP DRESS, Stevens- Johnson syndrome, toxic TEN, 혈액학적이상과같은중증에는절대시행해서는안된다. ENDA에서권고하는 BLs에대한비즉시형약물반응을진단하는알고리즘은그림 3과같다 6). 4. 교차반응의평가 BLs에대한비즉시형약물반응에서는 BL의중심구조 (core structure) 와전체분자 (core structure 와 side chain의 aminobenzyl group) 모두 T 세포에의해인지될수있다 41, 42). 하지만 amino-benzyl group이주요역할을한다. 최근에발표된바에의하면 43) aminopenicillins에반응을보인환자중 97.2% 가 amino-benzyl side chain이없는 cefpodoxime cephalosporins에문제없었으며, 71.8% 는 phenoxymethyl penicillin에문제가없었다. 이런결과들을볼때 penicillins과 cephalosporins 사이에는비즉시형반응에서의교차반응은매우드물다는것을알수있다. 기타약제들 1. 국소마취제 (local anesthetics:las) 에대한과민반응 LAs는전세계적으로매일 600만명이상이투여받고있으나실제로과민반응을극히적어서모등약물역작용중 1% 이내로알려져있다 44, 45). 다만자율신경계반응과독작용이잘못알레르기로진단되어치과치료등살아가는데매우중요한처치를받지못하는과진단이문제이다. LA는 lipophilic (aromatic group), intermediate chain linkage 와 hydrophilic (amino) group 의세부분으로구성되어있으며 intermediate chain 에따라 ester 혹은 amide 계분류되며 ( 표 3) 각각의계통별로는교차항원성이있으나아주드믄경우를제외하고는두계통간에교창항원성은없다고되어있다. 즉시형과세포매개형인비즉시형으로나타난다 46). 피부반응시험중피부단자시험의경우실제로즉시형반응이매우드물어서제외하자는의견들도있으나병력을참고로안전을 Table 3. Local anaesthetics are chemically either esters or amides Esters Benzocaine Chloroprocaine Cocaine (methylbenzoylecgonine) Procaine (novocaine) Proparacaine (alcaine) Tetracaine (amethocaine) Amides Articaine Bupivacaine Dibucaine (Cinchocaine) Etidocaine Levobupivacaine Lidocaine (Lignocaine) Mepivacaine Prilocaine Ropivacaine Sameridine Tonicaine From Thyssen JP, Menné T, Elberling J, Plaschke P, Johansen JD. Hypersensitivity to local anaesthetics - update and proposal of evaluation algorithm Contact Dermatitis. 59: Review 기하기위하여시행하는것을권하는그룹이더우세하다. 2. 조영제에대한반응 조영제에대한과민반응중 50% 는면역반응에의한것으로역시즉시형과비즉시형과민반응을야기한다 47, 48). 조영제에대한피부반응시험의민감도와특이도유용성에대하여서는아직확립된제안은없으나최근의보고들에의하면피부반응시험의특이도는 96~100% 며과민반응후 2~6 개월내에시행한피부반응시험에서는즉시형반응의경우 50%, 비즉시형인경우 47% 에서양성율을보였다. 교차항원성은비즉시형에서흔하여흥미로은사실은즉시형은 49%, 비즉시형은 52% 가이전에노출된적이없는환자들로이들에서의피부반응양성도가매우높았다 49). 이는이미조영제제노출이전에감작이되었다는것을의미한다. 따라서이전의개념과달리조영제에대한과민반응의진단에피부반응시험이의의가있을것으로판단되며, 앞으로이에대한좀더광범위한연구가필요하다. 결 약물알레르기의진단은임상적인병력, 피부반응시험, in vitro 검사, 약물유발시험으로진행된다. 이중기본적으로임상적인정보가가중요하여문진챠트의표준화작업이선행되어야한다. 즉시형은비즉시형에비하여피부반응의시험이유용성이크고실험실검사는아직두반응에서임상 론

7 - 대한내과학회지 : 제 76 권제 3 호통권제 583 호 에일상적으로적용하는데에많은어려움이있다. 약물알레르기를진단하고필요한약제를선택하기위해약물의교차항원성은매우중요하며이를위해서약물의중요항원이되는부분과구조적유사성에대한정보가필수적이다. 약물알레르기반응의확진은아직까지유발검사이며이는위험한전신반응을제외하고는전문가에의하여잘준비된환경에서점진적으로용량을조절하면서시행되어야한다. 약물알레르기기의진단은다기관, 다국적인차원에서증례들을모아서연구를해야하므로우리나라에서도서둘러이런표준화작업및범국가적인협동연구를진행해야할것이다. 중심단어 : 약물알레르기 ; 즉시형반응 ; 비즉시형반응 ; 피부반응시험 ; 교차반응 REFERENCES 1) Johansson SG, Bieber T, Dahl R, Friedmann PS, Lanier BQ, Lockey RF, Motala C, Ortega Martell JA, Platts-Mills TA, Ring J, Thien F, Van Cauwenberge P, Williams HC. Revised nomenclature for allergy for global use:report of the Nomenclature Review Committee of the World Allergy Organization, October J Allergy Clin Immunol 113: , ) Pichler WJ. Delayed drug hypersensitivity reactions. Ann Intern Med 139: , ) Bousquet PJ, Demoly P, Romano A. Drug allergy and hypersensitivity: still a hot topic. Allergy 64: , ) Bousquet PJ, Demoly P, Romano A, Aberer W, Bircher A, Blanca M, Brockow K, Pichler W, Torres MJ, Terreehorst I, Arnoux B, Atanaskovic-Markovic M, Barbaud A, Bijl A, Bonadonna P, Burney PG, Caimmi S, Canonica GW, Cernadas J, Dahlen B, Daures JP, Fernandez J, Gomes E, Gueant JL, Kowalski ML, Kvedariene V, Mertes PM, Martins P, Nizankowska-Mogilnicka E, Papadopoulos N, Ponvert C, Pirmohamed M, Ring J, Salapatas M, Sanz ML, Szczeklik A, Van Ganse E, De Weck AL, Zuberbier T, Merk HF, Sachs B, Sidoroff A. Pharmacovigilance of drug allergy and hypersensitivity using the ENDA-DAHD database and the GALEN platform. The Galenda project. Allergy 64: , ) Demoly P, Kropf R, Bircher A, Pichler WJ. Drug hypersensitivity questionnaire. Allergy 54: , ) Romano A, Demoly P. Recent advances in the diagnosis of drug allergy. Curr Opin Allergy Clin Immuno 7: , ) Adkinson NF, Bochner BS, Busse WW, Holgate ST, Lemanske RF, Simons ER. Middleton's Allergy: Principles and Practice, 7th Edition Elsevier Inc )Blanca M, Romano A, Torres MJ, Demoly P, DeWeck A. Continued need of appropriate betalactam- derived skin test reagents for the management of allergy to betalactams. Clin Exp Allergy 37: , ) Macy E. Penicillin skin testing in pregnant women with a history of penicillin allergy and group B streptococcus colonization. Ann Allergy Asthma Immunol 97: , ) Wong BB, Keith PK, Waserman S. Clinical history as a predictor of penicillin skin test outcome. Ann Allergy Asthma Immunol 97: , ) Blanca M, Romano A, Torres MJ, Férnandez J, Mayorga C, Rodriguez J, Demoly P, Bousquet PJ, Merk HF, Sanz ML, Ott H, Atanasković-Marković M. Update on the evaluation of hypersensitivity reactions to betalactams. Allergy. 64: , ) Levine BB, Ovary Z. Studies of the mechanism of the formation of the penicillin antigen III. The N(D-(benzylpenicilloyl)) group as an antigenic determinant responsible for hypersensitivity to penicillin G. J Exp Med 114:875, ) Rodriguez-Bada JL, Montañez MI, Torres MJ, Mayorga C, Canto G, Perez-Inestrosa E, Suau R, Blanca M. Skin testing for immediate hypersensitivity to betalactams: comparison between two commercial kits. Allergy 61: , ) Romano A, Viola M, Bousquet PJ, Gaeta F, Valluzzi R, Caruso C, Demoly P. A comparison of the performance of two penicillin reagent kits in the diagnosis of b-lactam hypersensitivity. Allergy 62:53-58, ) Romano A, Bousquet-Rouanet L, Viola M, Gaeta F, Demoly P, Bousquet JP. Benzylpenicillin skin testing is still important in diagnosing immediate hypersensitivity reactions to penicillins. Allergy. 64: , ) Blanca M, Vega JM, Garcia J, Carmona MJ, Terados S, Avila MJ, Miranda A, Juarez C. Allergy to amoxicillin with good tolerance to other penicillins. Study of the incidence in patients allergic to betalactams. Clin Exp Allergy 20: , ) Torres MJ, Romano A, Mayorga C, Moya MC, Guzman AE, Reche M, Juarez C, Blanca M. Diagnostic evaluation of a large group of patients with immediate allergy to penicillins: the role of skin testing. Allergy 56: , ) Jost BC, Wedner HJ, Bloomberg GR. Elective penicillin skin testing in a pediatric outpatient setting. Ann Allergy Asthma Immunol 97: , ) Antunez C, Blanca-Lopez N, Torres MJ, Mayorga C, Perez- Inestrosa E, Montañez MI,Fernandez T, Blanca M. Immediate allergic reactions to cephalosporins: Evaluation of crossreactivity with a panel of penicillins and cephalosporins. J Allergy Clin Immunol 117: , ) Romano A, Guéant-Rodriguez RM, Viola M, Amoghly F, Gaeta F, Guéant JL. Diagnosing immediate reactions to cephalosporins. Clin Exp Allergy 35: , ) Parker PJ, Parrinello JT, Condemi JJ, Rosenfeld SI. Penicillin

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<30322E20C6AFC1FD20B1E8BBF3C8C62E687770> 대한내과학회지 : 제 87 권제 6 호 2014 http://dx.doi.org/10.3904/kjm.2014.87.6.652 특집 (Special Review) - 약물알레르기 베타 - 락탐항생제알레르기및교차반응 을지대학교의과대학을지병원내과 김상훈 Beta-Lactam Allergy and Cross-Reactivity Sang-Hoon Kim Department